KORELASI ANTARA MIB-1, AgNOR DAN APOPTOSIS CASPASE-3 DENGAN RESPONS KEMORADIOTERAPI PADA KANKER SERVIK

Salah satu cara pengobatankanker servik adalah dengan kemoradioterapi melalui pemberian radioterapi dan kemoterapisecara bersamaan pada kanker servik stadium lanjut lokal. Respons kemoradioterapidipengaruhi oleh faktor biologis yaitu kinetika sel yang terdiri dari proliferasi dan kematian sel.Pada penelitian ini dipelajari korelasi antara biomarker proliferasi sel kanker, yaitu AgNOR, MIB-1, dan ekspresi apoptosis jalur caspase-3 dengan respons kemoradioterapi pada kanker servik.Dua puluh satu sediaan mikroskopik jaringan kanker servik yang diambil dari biopsi pasiensebelum menerima tindakan kemoradioterapi diberi pewarnaan AgNOR, sedangkan deteksiMIB-1 dan apoptosis caspase-3 dilakukan dengan teknik immunohistokimia. Setelah selesaimenerima kemoradioterapi dilakukan pengamatan respons klinik dengan cara pelvic control.Hasil penelitian menunjukkan bahwa sebelum kemoradioterapi tidak ditemukan korelasi nilaiAgNOR, MIB-1 dengan apoptosis (p>0,05). Proliferasi sel yang diamati dengan AgNOR danMIB-1 sebelum kemoradioterapi tidak menunjukkan adanya korelasi dengan respons jaringankanker setelah kemoradioterapi, namun ekspresi apoptosis menunjukkan korelasi positifdengan respons kemoradioterapi. Indeks apoptosis caspase-3 yang diperoleh dapat dijadikanbahan pertimbangan pada penjadwalan kemoradioterapi kanker servik

First Indonesian Nasopharyngeal Cancer Whole Epigenome Sequencing Identify Tumour Suppressor CpG Methylation

Handoko,1– 3 Marlinda Adham,2,4 Lisnawati Rachmadi,2,5 Demak Lumban Tobing,6 Asmarinah,7 Fadilah,8 Wei Dai,9,10 Anne Wing Mui Lee,10 Soehartati A Gondhowiardjo2,3 1Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 2Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Department of Radiation Oncology, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 4Department of Otorhinolaryngology - Head and Neck Surgery, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 5Department of Anatomical Pathology, Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 6Department of Clinical Pathology, Dharmais Cancer Hospital, Jakarta, Indonesia; 7Medical Biology Department, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia; 8Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia-Bioinformatics Core Facilities, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 9Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong (SAR), People’s Republic of China; 10Clinical Oncology Center, University of Hong Kong – Shenzhen Hospital, Shenzhen, People’s Republic of ChinaCorrespondence: Soehartati A Gondhowiardjo; Handoko, Email [email protected]: Nasopharyngeal cancer (NPC) is a multifaceted disease characterized by genetic and epigenetic modifications. While Epstein–Barr virus (EBV) infection is a known risk factor, recent studies highlight the significant role of DNA methylation in NPC pathogenesis. Aberrant methylation, particularly at CpG sites, can silence tumour suppressor genes, promoting uncontrolled cell growth. This study aims to analyse the methylation patterns in Indonesian NPC patients through whole-epigenome sequencing.Methods: Seven clinical nasopharyngeal cancer samples were collected and confirmed histopathologically. DNA was extracted, sequenced using Oxford Nanopore technology, and aligned to the GRCh38 human reference genome. Methylation analysis was performed using modkit and statistical analysis with R software. Enriched pathways and processes were identified using ClusterProfiler in R, and gene overlap analysis was conducted.Results: The analysis identified both globally hypermethylated and hypomethylated NPC samples. Key tumour suppressor genes, such as PRKCB, PLCB3, ITGB3, EPHA2, PLCE1, PRKCD, CDKN2A, CDKN2B, RPS6KA2, ERBB4, LRRC4, AKT1, PPP2R5C, and STK11 were frequently hypermethylated and confirmed to have lower expression in an independent NPC transcriptome cohort, suggesting their role in NPC carcinogenesis. Enriched KEGG pathways included PI3K-Akt signalling, ECM–receptor interaction, and focal adhesion. The presence of EBV DNA was confirmed in all samples, implicating its role in influencing methylation patterns.Discussion: This study provides comprehensive insights into the epigenetic landscape of NPC, underscoring the role of CpG methylation in tumour suppressor gene silencing. These findings pave the way for targeted therapies and highlight the need for region-specific approaches in NPC management.Keywords: nasopharyngeal cancer, epigenome, methylation, Epstein–Barr virus, whole-genome sequencin

Deteksi Sel Rogue Pada Sel Limfosit Darah Tepi Pasien Kanker Serviks Pra dan Paska Kemoradioterapi

Proses penentuan nilai dosis radiasi pengion berdasarkan indikator biologis atau biodosimetri umumnya dilakukan berdasarkan analisis kromosom disentrik. Proses biodosimetri berdasarkan analisis kromosom disentrik yang tidak boleh melibatkan kromosom disentrik dalam sel rogue karena nilai dosis yang diperoleh lebih tinggi dari nilai sebenarnya. Sel rogue adalah sel dalam tahap metafase yang berasal dari kultur sel limfosit darah tepi dan memiliki jumlah aberasi kromosom sangat tinggi meskipun sampel darah tidak terpapar oleh radiasi pengion. Hingga kini belum diketahui secara pasti penyebab timbulnya sel rogue dalam sel limfosit darah tepi. Terdapat Didugaan bahwa infeksi virus atau bakteri penyebab terbentuknya sel rogue. Dugaan lainnya menyatakan bahwa paparan radiasi dengan Linear Energy Transfer (LET) tinggi adalah penyebab timbulnya sel rogue. Tujuan penelitian adalah mendeteksi keberadaan sel rogue pada pasien kanker serviks sebelum dan sesudah dilakukan proses kemoradioterapi. Prediksi nilai dosis radioterapi dilakukan berdasarkan jumlah kromosom disentrik dengan atau tanpa melibatkan kromosom disentrik dalam sel rogue. Sebanyak 20 ml sampel limfosit darah tepi dari lima pasien kanker serviks paska radioterapi dikultur, dibuat preparatnya dan diamati. Hasil penelitian menunjukkan adanya satu sel rogue pada salah satu pasien kanker serviks paska kemoradioterap. yang diakibatkan oleh paparan radiasi. Prediksi dosis menunjukkan bahwa nilai prediksi dosis dengan melibatkan kromosom disentrik dalam sel rogue menyebabkan nilai dosis yang diperoleh lebih tinggi dari nilai sebenarnya. Berdasarkan hasil penelitian yang dilakukan dapat disimpulkan bahwa paparan radiasi pengion dapat mengakibatkan terbentuknya sel rogue pada individu dengan tingkat radiosensitivitas tinggi. Dengan demikian proses biodosimetri berdasarkan analisis kromosom disentrik tidak dapat dilakukan dengan melibatkan kromosom disentrik dalam sel rogue. The process of determining the ionizing radiation dose based on biological indicator or biodosimetry is generally carried out using the analysis of dicentric chromosome. Biodosimetry process based on the analysis of dicentric chromosome should not involving the dicentric in a rogue cell that may cause the radiation prediction doses value more higher than the true doses value. Rogue cells is cells in metaphase derived from the peripheral blood lymphocytes culture and contain a high number of chromosome aberration even though the blood sample were not exposed to ionizing radiation. Until now it was not clear what factor that can induce the rogue cells in peripheral blood lymphocytes. There was suggestion that infection of virus or bacteria and radiation exposure of high linear energy transfer (LET) can induce rogue cells. Aim of this research was to detect the presence of rogue cells in cervical cancer patients before and after radio chemotherapy process. The prediction of radiotherapy doses was carried out with and without involving the dicentric chromosomes in the rogue cells. Twenty milliliter of blood samples from five cervical cancer patients obtained before and after radiotherapy was cultured, harvested and analyzed. The experimental result showed that there was a presence of one rogue cell in one cervical cancer patient after radio chemotherapy process. A radiotherapy prediction doses showed that predictive dose value dose involving dicentric chromosomes in rogue cell was higher compared to the real radiation dose value. Based on the research result it can be concluded that exposure to ionizing radiation can induced the presence of the rogue cells in high radiosensitivity person. It means that in the biodosimetry process based on the analysis of dicentric chromosome should not involve the dicentric chromosome in the rogue cell

Pendeteksian Ekspresi Biomarker MNK Secara Semi Kuantitatif dan Kuantitatif Pada Kanker Serviks Sebelum Respon Kemoradioterapi

Kanker servik merupakan penyakit kanker yang umum dijumpai pada wanita yang disebabkan oleh virus HPV (Human Papilova Virus). Tujuan penelitian ini adalah untuk mengetahui hubungan ekspresi protein MNK (Mitogen Activated Protein Kinase) pada penderita kanker serviks sebelum tindakan pengobatan terhadap respon kemoradioterapi. Sampel uji yang digunakan adalah sediaan mikroskopis hasil biopsi jaringan kanker dari penderita kanker serviks stadium lanjut (IIB-IIIB) sebanyak 20 sampel. Metode yang digunakan adalah metode imunohistokimia dengan menggunakan biomarker MNK pada biopsi jaringan kanker serviks. Ekspresi protein MNK yang positif ditandai dengan warna coklat tua yang terdapat pada inti sel. Respon kemoradioterapi diperoleh dari RSUPN Dr. Cipto Mangunkusumo Jakarta dan RS Hasan Sadikin Bandung. Hasil penelitian menunjukkan nilai IRS (Imuno Reaktif Score) protein MNK pada grup respon kemoradioterapi baik lebih tinggi dibandingkan grup respon kemoradioterapi buruk dan tidak ditemukan adanya hubungan IRS protein MNK dengan respon kemoradioterapi. Sedangkan hubungan ekspresi MNK terhadap respon kemoradioterapi menunjukkan adanya korelasi perbedaan grup respon kemoradioterapi antara ekspresi protein MNK negatif dan ekspresi protein MNK positif. Cervical cancer is a cancer that common in women caused by HPV (Human Papilova Virus). The purpose of this study is to determine the relationship MNK protein expression (Mitogen-Activated Protein Kinase) in patients with cervical cancer before chemoradiotherapy treatment. Sample used was the preparation of microscopic cancer tissue biopsies from patients with advanced cervical cancer (IIB-IIIB) is 20 samples. The method used is immunohistochemistry using MNK biomarkers in cervical cancer tissue biopsies. MNK positive protein expression marked with dark brown color that is contained in the cell nucleus. Chemoradiotherapy response obtained from RSUPN Dr. Cipto Mangunkusumo and Hasan Sadikin Hospital in Bandung. The results show the value of the IRS (Immuno Reactive Score) MNK protein in response to chemoradiotherapy group either higher than the response to chemoradiotherapy group was bad and did not find any relationship IRS MNK protein with chemoradiotherapy response. While the relationship MNK expression responses show a correlation chemoradiotherapy group differences in chemoradiotherapy response between MNK expression negative and MNK expression positive

Pendeteksian Ekspresi Biomarker ERK Secara Semi Kuantitatif dan Kuantitatif Pada Kanker Serviks Sebelum Respon Kemoradioterapi

Kanker servik merupakan penyakit kanker yang umum dijumpai pada wanita yang disebabkan oleh virus HPV (Human Papilova Virus). Tujuan penelitian ini adalah untuk mengetahui hubungan ekspresi protein MNK (Mitogen Activated Protein Kinase) pada penderita kanker serviks sebelum tindakan pengobatan terhadap respon kemoradioterapi. Sampel uji yang digunakan adalah sediaan mikroskopis hasil biopsi jaringan kanker dari penderita kanker serviks stadium lanjut (IIB-IIIB) sebanyak 20 sampel. Metode yang digunakan adalah metode imunohistokimia dengan menggunakan biomarker MNK pada biopsi jaringan kanker serviks. Ekspresi protein MNK yang positif ditandai dengan warna coklat tua yang terdapat pada inti sel. Respon kemoradioterapi diperoleh dari RSUPN Dr. Cipto Mangunkusumo Jakarta dan RS Hasan Sadikin Bandung. Hasil penelitian menunjukkan nilai IRS (Imuno Reaktif Score) protein MNK pada grup respon kemoradioterapi baik lebih tinggi dibandingkan grup respon kemoradioterapi buruk dan tidak ditemukan adanya hubungan IRS protein MNK dengan respon kemoradioterapi. Sedangkan hubungan ekspresi MNK terhadap respon kemoradioterapi menunjukkan adanya korelasi perbedaan grup respon kemoradioterapi antara ekspresi protein MNK negatif dan ekspresi protein MNK positifCervical cancer is a cancer that common in women caused by HPV (Human Papilova Virus). The purpose of this study is to determine the relationship MNK protein expression (Mitogen-Activated Protein Kinase) in patients with cervical cancer before chemoradiotherapy treatment. Sample used was the preparation of microscopic cancer tissue biopsies from patients with advanced cervical cancer (IIB-IIIB) is 20 samples. The method used is immunohistochemistry using MNK biomarkers in cervical cancer tissue biopsies. MNK positive protein expression marked with dark brown color that is contained in the cell nucleus. Chemoradiotherapy response obtained from RSUPN Dr. Cipto Mangunkusumo and Hasan Sadikin Hospital in Bandung. The results show the value of the IRS (Immuno Reactive Score) MNK protein in response to chemoradiotherapy group either higher than the response to chemoradiotherapy group was bad and did not find any relationship IRS MNK protein with chemoradiotherapy response. While the relationship MNK expression responses show a correlation chemoradiotherapy group differences in chemoradiotherapy response between MNK expression negative and MNK expression positive

Hubungan gambaran spektral pulse wave doppler dengan respon klinis terapi radiasi eksternal pada kanker serviks stadium IIB-IVA

Tujuan: Mengetahui hubungan antara gambaran spektral Doppler USG transrektal Pulse Wave Doppler dengan respon klinis terapi radiasi eksternal pada kanker serviks stadium lokal lanjut (IIB-IVA). Metode: Menggunakan metode Prepost Design secara prospektif, dilakukan pemeriksaan Pulse wave Doppler menggunakan probe transrektal pada pasien kanker serviks stadium IIB-IVA. Pada pasien dilakukan pengukuran ukuran tumor secara ultrasonografi dan klinis sebagai ukuran awal tumor untuk menilai respon radiasi. Jumlah sampel adalah 60 untuk kelompok dengan hasil spektral Doppler baik dan buruk, yang dilakukan terapi radiasi eksternal dan dilakukan pengukuran masa kembali secara USG dan klinis untuk menentukan kriteria respon terapi. Hasil: Kelompok respon klinis buruk sebanyak 9 (75,0%) memiliki spektral vaskularisasi buruk dan sebanyak 3 (25,0%) memiliki spektral vaskularusasi baik sedangkan untuk respon klinis baik sebanyak 19(41,3%) memiliki spektral vaskularisasi buruk dan sebanyak 27 (58,7%) memiliki spektral vaskularisasi baik. Pada analisis dengan uji exact Fisher ditemukan hubungan yang bermakna (p<0,05) antara gambaran spectral PW Doppler transrektal dengan respon klinis terapi radiasi eksternal pada kanker serviks stadium IIB-IVA dengan nilai Relative Risk (RR) 3.214 kali. Kesimpulan: Terdapat hubungan yang bermakna antara gambaran spektral Doppler dengan respon klinis terapi radiasi eksternal pada kanker serviks stadium IIB-IVA.

Knowledge, attitude, and practices of midwives on premature rupture of membranes (PROM): A cross-sectional study in Samosir and Toba, Indonesia

Indonesia has a significantly higher maternal mortality ratio (MMR) than other countries in Southeast Asia, and infection is one of the most common causes of maternal deaths, of which premature rupture of membranes (PROM) can be the consequence of the infections. In primary healthcare settings, midwives play an important role in identifying and managing PROM appropriately; however, studies on their knowledge, attitudes, and practices related to PROM are limited. The aim of this study was to determine the midwives' knowledge, attitude and healthcare practice on PROM in Indonesia. A cross-sectional study was conducted among midwives at primary healthcare facilities in Samosir and Toba Regency, North Sumatra, Indonesia, from July to November 2022. The knowledge, attitude and practice towards PROM were assessed. Results showed that 57.5% of midwives had poor knowledge and 35.1% had poor attitude levels. There were 4.9% of midwives referred the patients immediately to the hospital. Our data indicated that aged 31−40 or 41−50 years, having a lower than bachelor degree and having a higher monthly number of referred PROM patients were significantly associated with poor knowledge compared to younger, having a bachelor degree, and lower monthly referral patient number, respectively. Similarly, younger, having higher degree and a having lower monthly referral number of PROM cases were associated with higher chances of having a sufficient-good attitude towards PROM. This study highlights that a significant percentage of midwives had poor levels of knowledge and attitude, and age, educational level and monthly referral number of PROM cases were associated with the level of knowledge and attitude

Predictive biomarkers of preeclampsia severity in a low resource setting: Role of red blood cell indices, NLR, and albumin-to-creatinine ratio

Preeclampsia (PE), a serious medical condition with substantial maternal and perinatal implications, poses a significant challenge, particularly in high-incidence countries like Indonesia. Red blood cell (RBC) indices, neutrophil-to-lymphocyte ratio (NLR), and microalbuminuria (albumin-to-creatinine ratio (ACR)) may signal systemic inflammation and endothelial dysfunction, recently recognized as potential indicators for diagnosing and predicting disease severity. The aim of this study was to analyze RBC indices, NLR, and ACR changes in women with PE and their potential for predicting disease severity. A cross-sectional study was conducted at multi-center hospitals across Medan, Indonesia, from June 2022 to June 2023. The patients were grouped into PE cases with and without severe features. Demographic characteristics and complications were recorded while blood and urine were tested. The Chi-squared test, Fisher's exact test and Mann-Whitney test were used to determine biomarkers associated with severe PE. A total of 208 PE patients were included in the study (104 patients for each PE with and without severe features). Our data indicated that PE patients with severe features had higher red cell distribution width (18.5% vs 13.7%; p&lt;0.001), NLR (5.66% vs 4.1%; p&lt;0.001), and ACR (755.97 mg/dL vs 468.63 mg/dL; p&lt;0.001) compared to those without severe features. In contrast, the platelet count was lower in severe features than those without (21.9 × 106/µL vs 27.0 × 106/µL; p=0.002). This study highlighted that PE patients with severe features predominantly had higher levels of RDW, NLR, and ACR and lower platelet counts compared to those without severe features. Therefore, basic tests such as complete blood count and urinalysis, which are inexpensive and feasible in primary care settings with limited resources, offer hope as valuable diagnostic biomarkers for pregnant women diagnosed with PE in a low resource setting

Role of estradiol and C-reactive protein levels on genitourinary syndrome in menopausal women

Menopause leads to decreased estradiol levels affecting tissue health and causing local inflammation in the genital organs and urinary tract. The rise of blood C-reactive protein (CRP) levels in menopausal women may indicate systemic inflammation associated with estradiol decline. The aim of this study was to determine the relationship between serum estradiol and CRP levels on genitourinary syndrome in menopausal women. A cross-sectional study was conducted among menopausal women who had not experienced menstruation for at least 12 consecutive months at Prof. dr. Chairuddin P. Lubis Hospital, Medan, Indonesia, in 2023. Estradiol and CRP levels were measured using enzyme-linked immunosorbent assay (ELISA) and the presence of genitourinary syndrome was assessed using the Menopause-Specific Quality of Life (MENQOL) questionnaire. The mean levels of estradiol and CRP were compared to menopausal women with and without genitourinary syndrome with the Mann-Whitney test. To assess the correlation between estradiol and CRP levels, and between their levels with the presence of genitourinary symptoms, the Spearman correlation test was used. The genitourinary syndrome was reported in 25% of the total included menopausal women. Our data indicated that the mean estradiol levels were not significantly different between menopausal women with and without genitourinary syndrome (9.13±2.47 pg/mL vs 18.96±31.23 pg/mL, p=0.881). The mean serum CRP level of menopausal women with genitourinary syndrome (9.72±6.30 mg/L) was higher than that of women without the syndrome (2.09±1.26 mg/L) with p&lt;0.001. In addition, serum CRP level, not estradiol, was correlated with the symptom score of genitourinary syndrome. This study highlights that to identify and manage genitourinary syndrome, monitoring of CRP levels is essential in menopausal women

Comparison of leptin and estrone levels between normal body mass index and obese menopausal women

Postmenopausal women often experience hormonal changes and shifts in fat composition, affecting weight gain and obesity. Understanding the link between hormones, especially estrogen and leptin, is key to managing weight and lowering disease risk in menopausal women. The aim of this study was to compare the levels of leptin and estrone in menopausal women with normal weight and obesity. A cross-sectional study was conducted on menopausal women, either normal body mass index (BMI) or obese, at H. Adam Malik General Hospital, Medan, Indonesia. Blood samples were collected to measure leptin and estrone levels using the enzyme-linked immunosorbent assay (ELISA) method. The differences in leptin levels between groups were analyzed using the Wilcoxon test, while the correlation between BMI and leptin was examined using the Pearson correlation test. The disparity in estrone levels in both groups was analyzed using the Mann-Whitney test and the correlations between variables were assessed using the Spearman or Pearson correlation tests as appropriate. The mean leptin levels in normal BMI and obesity groups were 17.73±4.96 and 25.46±12.95 ng/mL, respectively, and were statistically different (p=0.006). The mean estrone levels in menopausal women with normal BMI and obesity were 943.23±391.79 and 851.38±282.23 ng/mol, respectively and were not statistically different (p=0.564). A significant positive correlation was found between BMI and leptin level (r=0.59; p&lt;0.001), while  BMI and estrone were not significantly correlated (r=0.083; p=0.559). In conclusion, leptin level was significantly different between BMI groups and had a strong positive correlation with BMI. This finding could be an important insight in body weight management and disease risk prevention in menopausal women